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A Mutant of TTX-Resistant Cardiac Sodium Channels with TTX-Sensitive Properties
Abstract
The cardiac sodium channel α subunit (RHI) is less sensitive to tetrodotoxin (TTX) and saxitoxin (STX) and more sensitive to cadmium than brain and skeletal muscle (μl) isoforms. An RHI mutant, with Tyr substituted for Cys at position 374 (as in μl) confers three properties of TTX-sensitive channels: (i) greater sensitivity to TTX (730-fold); (ii) lower sensitivity to cadmium (28-fold); and (iii) altered additional block by toxin upon repetitive stimulation. Thus, the primary determinant of high-affinity TTX-STX binding is a critical aromatic residue at position 374, and the interaction may take place possibly through an ionized hydrogen bond. This finding requires revision of the sodium channel pore structure that has been previously suggested by homology with the potassium channel.
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Citations
Cited by
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Catterall, W. A. (2000) · Neuron · doi:10.1016/s0896-6273(00)81133-2 · Cited by 2,118
The Role of Voltage-Gated Sodium Channels in Pain Signaling
Bennett, D. L., Clark, A. J., Huang, J., Waxman, S. G., & Dib-Hajj, S. D. (2019) · Physiological Reviews · doi:10.1152/physrev.00052.2017 · Cited by 730
Overview of the voltage-gated sodium channel family
Yu (2003) · Genome biology · doi:10.1186/gb-2003-4-3-207 · Cited by 694
Resurgence of sodium channel research
Goldin, A. L. (2001) · Annual Review of Physiology · doi:10.1146/annurev.physiol.63.1.871 · Cited by 688
Dib-Hajj, S. D., Tyrrell, L., Black, J. A., & Waxman, S. G. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.15.8963 · Cited by 503
Metadata
- Authors
- Satin, J., Kyle, J. W., Chen, M., Bell, P., Cribbs, L. L., Fozzard, H. A., & Rogart, R. B.
- Venue
- Science
- Published
- 1992-05-22
- Volume
- 256
- Issue
- 5060
- Pages
- 1202-1205
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2093297294
- Cited by
- 389
- References
- 0
- FWCI
- 8.53
- Type
- journal article
- Language
- en
- Open access
- closed
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- Satin, J., Kyle, J. W., Chen, M., Bell, P., Cribbs, L. L., Fozzard, H. A., & Rogart, R. B. (1992). A Mutant of TTX-Resistant Cardiac Sodium Channels with TTX-Sensitive Properties. Science. https://doi.org/10.1126/science.256.5060.1202
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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